This invention generally relates to pharmaceuticals and more specifically to a method and compositions for treating patients with sexual impotence.
Sexual impotence in males may be defined as a failure of penile erection accompanied at times by a failure of ejaculation and orgasm. The known causes for this disability are related to conditions involving failure of male hormone production and are rare. For the majority of cases no hormonal or primary structural defects are clinically demonstrable. Such instances have been considered by exclusion to be on a "vasculogenic" basis, or due to a failure or abnormality of neural control of the genital vasculature, possibly arising from central nervous system dysfunction and possibly involving psychogenic factors. This common type of impotence usually increases in frequency with advancing age.
Alpha-1 receptors have a number of functions in the sympathetic nervous system, including mediation of ejaculation. Located at the postsynaptic effector sites in smooth muscle and gland cells, stimulation of these alpha-1 receptors by norepinephrine causes an excitatory response. In arteries, such stimulation results in constriction of the blood vessels and an increase in blood pressure. Alpha-2 receptors, located at presynaptic effector sites in smooth muscle and gland cells, mediate feedback inhibition of neural release of norepinephrine. There are also post-synaptic extrajunctional alpha-2 receptors, located nearer to the vascular intima which transduce vasoconstriction in response to circulating epinephrine or norepinephrine. Stimulation of beta-1 receptors, located predominantely in the heart, causes an increase in heart rate and cardiac contractility. Beta-2 receptors, located primarily in smooth muscle and gland cells, evoke inhibitory responses when stimulated such as dilatation of arteries causing a decrease in blood pressure.
Knowledge of these receptors and their functions has been used to develop a number of pharmacological agents. Most notably, antihypertensive drugs, referred to as adrenergic blocking drugs, have been produced which block alpha-1 receptors and beta-1 receptors by blocking the effect of the neurotransmitters adrenaline (epinephrine) and noradrenaline (norepinephrine) in the sympathetic nervous system. The alpha-1 blockers cause vasodilatation while the beta-1 blockers decrease heart rate and cardiac contractility, all responses which cause a decrease in blood pressure. Conversely, beta-2 blockers reduce flow to muscles and favor bronchial constriction.
While these drugs can be effective in controlling blood pressure, they are often accompanied by a number of deleterious side effects, including impotence. Examples of commonly used antihypertensive drugs which cause impotence include the alpha blockers, beta blockers, and centrally acting anti-adrenergic medications such as methyldopa, clonidine, reserpine, and guanabenz. (Gilman, A., et al., The Pharmacological Basis of Therapeutics 177 (1990)). Since hypertension is a common illness of the sexually active population, the risk of impotence is an important consideration when putting these patients on antihypertensive medications. Some patients who experience impotence while taking such medications will independently discontinue them rather than be deprived of their ability to have sex, ignoring the possibility of heart attack and stroke from uncontrolled hypertension. Unfortunately, the value placed on sex outweighs concern about uncontrolled hypertension in these understandably frustrated patients. Furthermore, there is no known cure for impotence of the type lacking a demonstrable organic cause.
It is therefore an object of the present invention to provide a method and composition for treating impotence in patients who have no demonstrable organic cause for the disorder.
It is a further object of the present invention to provide a method and composition for treating patients with impotence caused iatrogenically by medications such as antihypertensives.